Pharmaceutical formulations are presented in a variety of different packaging, including packaging made of glass, metal, plastic and natural materials. For liquid formulations, e.g. solutions or suspensions, the packaging must be and remain sealed to prevent leakage. However, a number of technical and practical difficulties exist with all such containers.
It is known to administer drugs to the lungs of a patient using a nebuliser, allowing a patient to administer the drug whilst breathing normally. The drugs are provided in a unit dose ampoule (UDA), containing a relatively small volume, typically 1 mL-5 mL, of solution and typically made of plastics material. A method of making ampoules is by Blow-Fill-Seal (BFS), under aseptic conditions, in which the ampoule is formed by extrusion and filled with solution in a multi-part but essentially one-step process. If necessary, and provided the contents are not heat labile, heat sterilization can be used, e.g. ampoules can be sterilised by terminal sterilisation methods, i.e. after the ampoule has been filled and sealed. These methods are well established and accepted by regulatory authorities worldwide.
A known problem with existing ampoules is that they allow oxygen, other gases and other volatile compounds into the ampoule and allow water (moisture) to exit. Testing of the contents has revealed that, during storage, contaminants can pass through the plastic of ampoule walls and be absorbed into the formulation. As one specific example, unacceptable amounts of vanillin have been found inside ampoules, leading to failure of the product and refusal of regulatory authorities to license the ampoules without safeguards against this external contamination.
The US FDA has recently required that ampoules be over-wrapped by a sealing pouch to avoid environmental contamination of the ampoule contents. The pouch material is typically a tri-laminate of paper and/or polymer, aluminium and low density polyethylene (LDP). This pouch is regarded as an acceptable solution but the contents are still susceptible to oxidation over time. This is particularly an issue with drug formulations containing oxygen sensitive materials.
It is known to carry out the blow-fill-seal method of making and filling ampoules using nitrogen rather than sterile air during as many steps as possible in the process. Nitrogen can be used to cap the solution in the ampoule. Nitrogen can be introduced into the pouch at the time the ampoules are sealed inside the pouch. It is, however, a problem that using nitrogen in this process requires specialised equipment or modification of existing equipment. Health and safety precautions associated with the use of nitrogen tend to increase production costs and times and the efficiency of nitrogen entrapment within the pouch varies and is not totally efficient
An object of the present invention is to solve or at least ameliorate the above-identified issues. An object of preferred embodiments of the invention is to provide alternative, more preferably improved methods of storing ampoules within sealed containers and to provide alternative, preferably improved sealed containers containing ampoules.